dc.contributor.author | Hu, Chih-Chi Andrew | |
dc.contributor.author | Dougan, Stephanie K. | |
dc.contributor.author | McGehee, Annette M. | |
dc.contributor.author | Ploegh, Hidde | |
dc.contributor.author | Love, John C | |
dc.date.accessioned | 2012-10-25T20:20:49Z | |
dc.date.available | 2012-10-25T20:20:49Z | |
dc.date.issued | 2009-04 | |
dc.date.submitted | 2009-02 | |
dc.identifier.issn | 0261-4189 | |
dc.identifier.issn | 1460-2075 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/74263 | |
dc.description.abstract | XBP-1, a transcription factor that drives the unfolded protein response (UPR), is activated in B cells when they differentiate to plasma cells. Here, we show that in the B cells, whose capacity to secrete IgM has been eliminated, XBP-1 is induced normally on induction of differentiation, suggesting that activation of XBP-1 in B cells is a differentiation-dependent event, but not the result of a UPR caused by the abundant synthesis of secreted IgM. Without XBP-1, B cells fail to signal effectively through the B-cell receptor. The signalling defects lead to aberrant expression of the plasma cell transcription factors IRF4 and Blimp-1, and altered levels of activation-induced cytidine deaminase and sphingosine-1-phosphate receptor. Using XBP-1-deficient/Blimp-1-GFP transgenic mice, we find that XBP-1-deficient B cells form antibody-secreting plasmablasts in response to initial immunization; however, these plasmablasts respond ineffectively to CXCL12. They fail to colonize the bone marrow and do not sustain antibody production. These findings define the role of XBP-1 in normal plasma cell development and have implications for management of B-cell malignancies. | en_US |
dc.description.sponsorship | National Science Foundation (U.S.). Graduate Research Fellowship Program | en_US |
dc.description.sponsorship | Cancer Research Institute (New York, N.Y.) (Fellowship) | en_US |
dc.language.iso | en_US | |
dc.publisher | Nature Publishing Group | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1038/emboj.2009.117 | en_US |
dc.rights | Creative Commons Attribution | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/ | en_US |
dc.source | PMC | en_US |
dc.title | XBP-1 regulates signal transduction, transcription factors and bone marrow colonization in B cells | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Hu, Chih-Chi Andrew et al. “XBP-1 Regulates Signal Transduction, Transcription Factors and Bone Marrow Colonization in B Cells.” The EMBO Journal 28.11 (2009): 1624–1636. © 2012 European Molecular Biology Organization | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Biology | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Chemical Engineering | en_US |
dc.contributor.department | Whitehead Institute for Biomedical Research | en_US |
dc.contributor.mitauthor | Hu, Chih-Chi Andrew | |
dc.contributor.mitauthor | Dougan, Stephanie K. | |
dc.contributor.mitauthor | McGehee, Annette M. | |
dc.contributor.mitauthor | Love, J. Christopher | |
dc.contributor.mitauthor | Ploegh, Hidde | |
dc.relation.journal | EMBO Journal | en_US |
dc.eprint.version | Final published version | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dspace.orderedauthors | Hu, Chih-Chi Andrew; Dougan, Stephanie K; McGehee, Annette M; Love, J Christopher; Ploegh, Hidde L | en |
dc.identifier.orcid | https://orcid.org/0000-0003-0921-3144 | |
dc.identifier.orcid | https://orcid.org/0000-0002-1090-6071 | |
mit.license | PUBLISHER_CC | en_US |
mit.metadata.status | Complete | |